Pteroylglutamic acid (30 mg/ml) in 0.3 M NaHCO3 (final pH 7.6), injected intraperitoneally into 40-day-old male Charles River mice (200 ug/gm body weight) produces microscopic and physiologic damage identical to the clinical complex of acute tubular necrosis. The renal response to this acute injury is characterized by a transient increase in bulk renal weight (plus 85 percent), protein (plus 20 percent), RNA (plus 65 percent) and DNA (plus 75 percent). Simultaneous administration of Lasix (25 ug/gm body weight) and Folic acid decreases not only the histologic damage but also the magnitude of the metabolic chages. In vivo data indicate that diuretics with alkalinization reduce the extent of renal injury and simultaneously the degree of expected renal growth or repair. The observations support the clinical practice of initiating agressive diuresis in the face of progressing, recently established acute tubular necrosis to modify the ultimate degree of tubular injury. Preliminary studies exposing renal tubular epithelium from adult Charles River mice in vitro to Folic acid ((10 ug/ml) results in immediate increase in DNA synthesis with a maximal increase in DNA of plus 75 percent within 24 hours after exposure. Preliminary studies indicate that Folic acid in vitro does initiate a transient increase in DNA synthesis, and that this in vitro system can be employed to determine the cellular response to growth stimuli.